Considerable data are now available regarding the radiation responsiveness of neural precursor cells that exist in the neurogenic regions of the mammalian forebrain. These cells and their progeny are extremely sensitive to irradiation, undergoing apoptosis after clinically relevant doses that do not result in overt tissue injury. In addition, there is compelling evidence that radiation significantly affects the whole process of neurogenesis and that the sensitivity depends, at least in part, on alterations in the microenvironment within which the precursor cells exist. Although provocative data exist suggesting that inflammation, oxidative stress, or morphologic relations influence neurogenesis, the precise mechanisms involved remain obscure and need to be investigated. Additionally, it is important to try to understand what these findings may mean in the context of radiation paradigms associated with the treatment of intracranial disease. Understanding how neural precursor cells respond to noxious stimuli is likely to lead to new therapeutic approaches that should restore neurogenesis and perhaps improve cognitive performance.